The
antibiotic combination of
sulfamethoxazole and
trimethoprim was evaluated for treatment of
peritonitis in patients in
renal failure undergoing
continuous ambulatory peritoneal dialysis. Although current methods of analysis were adequate for measurement of
sulfamethoxazole, a review of the available methods of analysis for
trimethoprim did not yield a satisfactory method. Therefore, a high performance liquid chromatography (HPLC) assay was developed to follow the pharmacokinetics of
trimethoprim in serum and peritoneal
dialysate fluid. In this assay,
trimethoprim is extracted from plasma, serum, or
dialysate fluid by solid-phase column chromatography that is efficient (82% recovery), quick, and simple to use. The HPLC method utilizes a common reverse-phase system with a 0.01 M
sodium acetate and
acetonitrile mobile phase and detection at 254 nm. The assay offers excellent between-run replication (p = 0.96), high sensitivity (0.05 microgram/mL), and linearity over a wide range (2-100 micrograms/ml; r = 0.99). The method offers freedom from interference by metabolites and a wide range of commonly administered drugs. It is suitable for other pharmacokinetic studies involving
trimethoprim but not its metabolites, and also for clinical assay of
trimethoprim in situations where high levels of the
antibiotic are necessary to combat resistant organisms and in serious
infections by opportunistic organisms such as Pneumocystis carinii.